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A Mangia

Publications and source records attributed to A Mangia.

At least 19 recordsLinked to original sources

Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer.

PURPOSE: The prospective applicability of new biologic tumor information to personalize adjuvant treatment of women with operable breast cancer remains to be demonstrated. The aim of the present study was to investigate whether patients with fast-proliferating, node-negative breast cancer could benefit from adjuvant chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC). PATIENTS AND METHODS: Beginning in November 1989, we analyzed the proliferative activity of primary tumors in a consecutive series of women with node-negative breast cancer to identify subgroups of patients with a worse prognosis and who were therefore suitable candidates for adjuvant systemic therapy. Proliferative activity was determined by means of the [3H]-thymidine incorporation assay using an autoradiographic technique. Women with fast-proliferating breast cancer ([3H]-thymidine labeling index, > 2.3%) were randomized to receive either six cycles of adjuvant FEC or no adjuvant therapy until disease progression. RESULTS: One-hundred twenty-five and 123 patients treated with radical surgery for pT1 to T2, N0, M0 breast cancer were randomized to the FEC and control arms, respectively. After a median follow-up of 70 months, 27 events (21.6%) were observed in the FEC arm and 39 (32.2%) in the control arm, with a significantly lower number of locoregional relapses in the FEC group. Five-year disease-free survival (DFS) was 81% in the FEC group and 69% in the control group (P <.02 by log-rank test). Cox multivariate analysis described the impact of adjuvant therapy with FEC on DFS as independent of the patients' main clinical-pathologic characteristics. CONCLUSION: FEC adjuvant polychemotherapy seems able to significantly improve the clinical outcome of patients with fast-proliferating, node-negative breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Supercritical fluid extraction for liquid chromatographic determination of carotenoids in Spirulina Pacifica algae: a chemometric approach.

An experimental design procedure was used to investigate the effects of some operating parameters on the supercritical fluid extraction of carotenoids beta-carotene, beta-cryptoxanthin and zeaxanthin from Spirulina Pacifica algae, a carotenoid-rich dietary product. Variables tested were temperature and pressure of the supercritical fluid, dynamic extraction time and percentage of ethanol added as the modifier. Each variable was tested at three levels; 31 experiments were performed in random order. Analyses of the extracts were performed by high-performance liquid chromatography with UV-Vis photodiode array detection. Analytical responses (chromatographic peak areas) were processed by using a stepwise multiple regression analysis, in order to find polynomial functions describing the relationships between variables and responses. For all the analytes the experimental conditions providing the highest extraction yield inside the experimental domain considered were found. Supercritical fluid extraction results obtained in these conditions were compared with those obtained by performing solvent extraction in order to evaluate the effectiveness of the supercritical fluid extraction procedure.

Carotenoids↗

Predictability of monthly and yearly rhythms of breast cancer features.

In order to evaluate if breast cancer biological characteristics undergo significant menstrual and seasonal variations, we analysed in a consecutive series of 905 breast cancer patients, steroid receptor level (ER and PgR by DCC assay), proliferative activity (3H-Thymidine Labeling Index, 3H-TLI) and size of primary tumour in relation to calendar date and day of menstrual cycle at the time of the surgical procedure. For data analysis, the method of time series construction and classical spectral analyses with Bartlett Kolmogorov-Smirnov test for white noise (BKS test) was utilised. For what concerns menstrual variations, 3H-TLI showed a significant periodicity (t = 0.3146, p < 0.01 by BKS test) with peaks at day 12nd and day 18th; ER showed a significant periodicity (t = 0.3605, p < 0.01 by BKS test) with more evident peak at day 27th; PgR, a significant periodicity (t = 0.160, p = 0.05 by BKS test) with peaks at day 15th and day 24th, similar to that observed for tumour size (t = 0.19, p < 0.05 by BKS test). With respect to yearly fluctuations, 3H-TLI showed only a trend for a significant rhythm (t = 0.16, p = 0.06 by BKS test) with peaks in May and November; ER a significant periodicity (t = 0.2099, p < 0.05 by BKS test) with two evident peaks in January and April; also for PgR a significant periodicity (t = 0.3161, p < 0.05 by BKS test) was demonstrated with a peak in July; finally, tumour size showed a significant rhythm (t = 0.335, p < 0.01) paralleling 3H-TLI behaviour. Finally, the analysis of variance with interaction of menstrual and seasonal timings showed that only the seasonal timing was able to independently influence the 3H-TLI variations (3H-TLI higher in spring). We confirmed that breast biology has significant menstrual and seasonal variations and that the seasonality is probably the timing factor more relevant in periodicity determination.

Breast Neoplasms↗

A randomized trial of amantadine and interferon versus interferon alone as initial treatment for chronic hepatitis C.

The aim of this study was to compare, in an open-label study, the efficacy and safety of a combination of interferon (IFN) and amantadine (AMA) with that of IFN alone in previously untreated patients with chronic hepatitis C. A total of 200 patients were randomized to 6 MU of IFN-alpha2a 3 times per week, with 200 mg of AMA daily (n = 99) or to an identical dose of interferon alpha2a (n = 101). Patients were treated for 12 months and observed for 6 months' posttreatment. At the completion of treatment, 28.7% of patients in the monotherapy group and 45.5% in the combination group had a virologic response (P =.014). At 6 months' posttreatment, a sustained virologic response was observed in 16.8% (95% CI: 9-23) of patients with IFN alone versus 29.3% (95% CI: 19-37) of patients who were treated with combination therapy (P =.036). In each of the 2 treatments, genotype was the only predictive parameter for a sustained response. At the logistic regression analysis, therapy and genotype were the only 2 parameters with an independent predictive value. In the combination group, at examination of month 3, hepatitis C virus (HCV)-RNA status had a 97.6% (95% CI: 93-102) positive predictive value and a 50% (95% CI: 37-63) negative predictive value for a sustained virologic clearance. A substantial proportion of naïve patients with chronic hepatitis C have an end-of-treatment and end-of-follow-up virologic and biochemical response to a combination of IFN and AMA. This new treatment appears safe and well tolerated.

Adult↗

Spectrophotometric and coulometric detection in the high-performance liquid chromatography of flavonoids and optimization of sample treatment for the determination of quercetin in orange juice.

The capabilities of spectrophotometric and electrochemical detection techniques were investigated for the high-performance liquid chromatographic determination of flavonoids. Liquid chromatographic analyses were performed on eleven compounds belonging to three different classes of flavonoids: flavanone glycosides, flavone and flavonol aglycones. Separation of all compounds examined was carried out under reversed-phase conditions on a C18 narrow-bore column for UV detection, whereas for electrochemical detection, a C18 standard-bore column was used. UV analyses were carried out at 280 nm for flavanones and at 265 nm for flavones and flavonols, whereas controlled-potential coulometric measurements were performed using a porous graphite electrode. Analytical performances of the methods were compared in terms of linearity, limits of detection (LODs) and precision. Linearity over two orders of magnitude and LODs at low-ppm levels (0.06-1 mg/l) were demonstrated for all techniques considered. Instrumental precision in terms of relative standard deviation was found to be between 0 and 5% for the liquid chromatography (LC)-UV system and between 0.6 and 10% for the LC-electrochemical detection (ED) system. The methods developed were applied to the analysis of flavanones and flavonols in a real sample, such as an extract of orange juice. Even though quercetin glycoside is mostly present in orange juice as rutin, other different glycosides of this flavonol could be present; on this basis, the hydrolysis of all glycosides to aglycone allows one to obtain more accurate data on the flavonol concentration in orange juice. To avoid sample degradation and to increase extraction efficiency, quercetin hydrolysis was optimized using a central composite design to investigate the effects of acid concentration and hydrolysis time on extraction recovery.

Beverages↗

Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis.

BACKGROUND: The identification of therapeutic agents that can prevent the pancreatic injury after endoscopic retrograde cholangiopancreatography (ERCP) is of considerable importance. METHODS: We performed a meta-analysis including 28 clinical trials on the use of somatostatin (12 studies), octreotide (10 studies), and gabexate mesilate (6 studies) after ERCP. Outcome measures evaluated were the incidence of acute pancreatitis, hyperamylasemia, and pancreatic pain. Three analyses were run separately: for all available studies, for randomized trials only, and for only those studies published as complete reports. RESULTS: When all available studies were analyzed, somatostatin and gabexate mesilate were significantly associated with improvements in all three outcomes. Odds ratios (OR) for gabexate mesilate were 0.27 (95% CI [0.13, 0. 57], p = 0.001) for acute pancreatitis, 0.66 (95% CI [0.48, -0.89], p = 0.007) for hyperamylasemia, and 0.33 (95% CI [0.18, 0.58], p = 0. 0005) for post-procedural pain. Somatostatin reduced acute pancreatitis (OR 0.38: 95% CI [0.22, 0.65], p < 0.001), pain (OR 0. 24: 95% CI [0.14, 0.42], p < 0.001), and hyperamylasemia (OR 0.65: 95% CI [0.48, 0.90], p = 0.008). Octreotide was associated only with a reduced risk of post-ERCP hyperamylasemia (OR 0.51: 95% CI [0.31, 0.83], p = 0.007) but had no effect on acute pancreatitis and pain. The statistical significance of data did not change after analyzing randomized trials only or studies published as complete reports. For each considered outcome, the publication bias assessment and the number of patients that need to be treated to prevent one adverse effect were, respectively, higher and lower for somatostatin than for gabexate mesilate. CONCLUSIONS: The pancreatic injury after ERCP can be prevented with the administration of either somatostatin or gabexate mesilate, but the former agent is more cost-effective. Additional studies comparing the efficacy of short-term infusion of somatostatin versus gabexate mesilate in patients at high risk for post-ERCP complications seem warranted.

Acute Disease↗

Validation of a liquid chromatography ionspray mass spectrometry method for the analysis of flavanones, flavones and flavonols.

The application of liquid chromatography/mass spectrometry (LC/MS) with a TurboIonspray (TIS) interface was investigated as a new method for the analysis of flavonoids. Eleven compounds belonging to three different classes of flavonoids were studied: eriocitrin, neoeriocitrin, naringin, narirutin, hesperidin, neohesperidin (flavanone glycosides), quercetin, kaempferol, galangin (flavonol aglycones), chrysin, apigenin (flavone aglycones). Chromatographic separations were performed under reversed-phase conditions using a C18 narrow-bore LC column; a mixture of an aqueous solution of formic acid (pH 2.4) and acetonitrile was used as the mobile phase. Isocratic elution was operated in the case of flavanones, whereas gradient elution was used for the simultaneous separation of flavones and flavonols. The adaptability of TIS to high flow applications allows the use of LC eluent flow rates at 200 µL/min without post-column splitting. Qualitative analysis was performed in negative-ion (NI) full-scan mode, whereas response linearity, detection limits and precision of the method were studied under NI selected ion monitoring (SIM) conditions. Characterization of isomers differing in the glycosylation was found to be possible on the basis of different mass spectra. Detection limits in the low-ng range (0.08-0.4 ng) were found, about twenty-fold lower than those reported previously. The method was applied to identify and determine the content of flavonoids in an orange juice sample. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

Liquid chromatography-electrospray mass spectrometry of beta-carotene and xanthophylls. Validation of the analytical method.

The investigation of beta-carotene and the xanthophylls beta-cryptoxanthin, lutein, zeaxanthin, canthaxanthin and astaxanthin using reversed-phase liquid chromatography-electrospray mass spectrometry interfaced with TurboIonspray (LC-TurboISP-MS) is described. Two narrow-bore C18 columns connected in series and an isocratic solvent system containing acetonitrile-methanol (0.1 M ammonium acetate)-dichloromethane at a flow-rate of 300 microl/min (without splitting) were used. Operating in the positive-ion mode over m/z 500-650, the effects on the formation of the molecular ion species or adduct ions and the MS detector response were investigated for carotenoids, varying the orifice plate voltage, the ring voltage and the ISP voltage. Both conventional ISP and TurboISP were performed; using the TurboISP-MS system, ionization efficiency increased with respect to ISP-MS, particularly at the highest temperature (500 degrees C). Good results were particularly obtained for beta-carotene, which was detectable at the low ng level, without the use of solution-phase oxidants. Using LC columns and acquiring in single-ion monitoring mode, detection limits were estimated to be in the 0.1-1 ng range; dynamic range was established between one- and two-orders of magnitude. Better sensitivity under positive-ion than negative-ion conditions was demonstrated.

Chromatography, High Pressure Liquid↗

Lack of hepatitis C virus replication intermediate RNA in diseased skin tissue of chronic hepatitis C patients.

The extent of extrahepatic hepatitis C virus (HCV) replication seems to be low-level and confined to cells of hematopoietic lineage. However, given the spectrum of extrahepatic manifestations associated with HCV, several tissues other than the liver have been suggested as targets of HCV replication and damage. The presence and level of HCV RNA were examined in 19 skin tissue samples from patients chronically infected with HCV and referred for lichen ruber planus (n = 11) or cutaneous vasculitis associated with mixed cryoglobulinemia (n = 8). Serum HCV RNA was quantitated and genotyped by assays that are available commercially. Tissue HCV RNA of genomic- and minus-strand polarity was titrated by a strand-specific semiquantitative RT-PCR. Low titers of genomic-strand HCV RNA were found in three skin specimens from patients with cutaneous vasculitis due to mixed cryoglobulinemia, but in none with lichen ruber planus. The replication intermediate HCV RNA was not detected in any of the skin tissues examined, independent of the serum HCV RNA level or genotype. It is concluded that the occurrence of cutaneous vasculitis and lichen ruber planus in chronic hepatitis C patients is unlikely to be due to HCV replication in the skin.

Adult↗

HLA class II favors clearance of HCV infection and progression of the chronic liver damage.

BACKGROUND/AIMS: This study was aimed to determine whether host-dependent genetic factors modulate the outcome of HCV infection. METHODS: HLA class II DRB and DQB typing was performed in 184 infected patients and 200 healthy volunteers. Among the patients, 149 subjects had persistent HCV viremia (Group 1) and 35 subjects underwent spontaneous viral clearance (Group 2). Group 1 included cirrhotic patients with transfusion-acquired infections (n = 79), asymptomatic HCV carriers (n = 42), and patients with chronic hepatitis C responsive to interferon therapy (n = 28). RESULTS: Spontaneous viral clearance was associated with HLA DRB1*1104 (pc = 0.054, OR = 4.51, 95% C.I. 2.02-10.1) and HLA DQB1*0301 (pc = 0.0039, OR = 4.52, 95% C.I. 2.15-9.51). In Group 1 the haplotype DRB1*1104/DQB1*0301 was less frequent (4.8%) than in Group 2 (18.3%) (pc = 0.009, OR = 7.38, 95% C.I. 2.58-21.59). At the HLA level, cirrhotic patients were not different from asymptomatic HCV carriers and patients with interferon-induced viral clearance. In cirrhotic patients infected with genotype 1b, the DQB1*0502 allele was more frequently found in those with rapidly progressive liver damage (OR = 8.15, 95% C.I. 1.49-44.44), but the corrected p-value was not significant (pc = 0.09). CONCLUSIONS: The HLA haplotype DRB1*1104/DQB1*0301 appears to contribute to the spontaneous clearance of HCV infection. The predominance of the DQB1*0502 allele in cirrhotic patients with a rapidly progressive disease possibly reflects an influence of this allele on the progression of the HCV-related liver disease.

Adult↗

Anticardiolipin antibodies in patients with liver disease.

OBJECTIVE: Our aim was to test the hypothesis that anticardiolipin antibodies (aCL) may cause an antiphospholipid syndrome and thrombotic events in patients with liver disease. METHODS: aCL were measured in 116 healthy controls and 372 patients with liver disease of different stage and etiology: 136 cases secondary to hepatitis C virus (HCV) infection, 139 due to hepatitis B virus (HBV) infection, 69 with alcoholic liver damage, and 28 cryptogenic in origin. Prior thrombotic events were recorded. The results were related to age, gender, stage, severity, and etiology of the liver disease, as well as to the occurrence of organ- and nonorgan-specific autoantibodies. RESULTS: aCL were positive in 4.4% of controls and in 18.8% of patients (p < 0.0002). Patients with aCL were more frequently men with an advanced cirrhosis and simultaneous occurrence of anti-smooth-muscle antibodies (ASMA) in serum (p < 0.0006); their liver damage was often secondary to HBV (37.3%) or alcohol abuse (18.5%). At conditional logistic regression analysis, only the presence of ASMA (odds ratio [OR] = 3.02, 95% confidence interval [CI] 1.7-5.5, p = 0.0003), HBV (OR = 3.4, 95% CI 1.6-7.2, p = 0.0013), or alcoholic liver disease (OR = 5.3, 95% CI 2.3-12.2, p = 0.0001) were independently associated with aCL. Thrombosis was encountered in 24 patients (6.4%). At conditional logistic regression analysis, thrombosis was significantly associated with advanced age (OR = 1.07, 95% CI 1.0-1.1, p = 0.0094), development of hepatocellular carcinoma (OR = 17.8, 95% CI 1.6-196.0, p = 0.01), HBV etiology (OR = 6.3, 95% CI, 1.6-24.6, p = 0.0076), or cryptogenic liver disease (OR = 54.8, 95% CI 5-599.9, p = 0.001). Of the five patients with newly documented portal thrombosis during the follow-up, only one tested positive for aCL. CONCLUSIONS: In patients with nonautoimmune liver disease, aCL production is an epiphenomenon of the liver damage and is not associated with thrombotic complications. These data do not support the hypothesis that HCV is a cause of the antiphospholipid syndrome.

Antibodies, Anticardiolipin↗

HCV and diabetes mellitus: evidence for a negative association.

OBJECTIVE: Uncontrolled, retrospective clinical studies have recently claimed that HCV infection could trigger the onset of diabetes mellitus (DM). We sought to verify the association between DM and liver diseases of different etiology, stage, and severity in a prospective study including gender- and age-matched controls. METHODS: Two hundred forty-seven patients with liver cirrhosis (184 men, 116 with an associated hepatocellular carcinoma, 34% in Child-Pugh's class A) were evaluated (group 1). One hundred fifty-seven (63.5) of them were HCV positive, 38 (15.5%) HBV positive, 49 (19.8%) alcohol abusers, and three (1.2%) cryptogenic. Two control groups were also included. The first control group consisted of 138 patients with chronic hepatitis due to HCV infection (73.9%), HBV infection (15.9%), or alcohol abuse (10.2%) (group 2). The second control group included 494 patients with an acute osteoarticular trauma, age- and gender-matched with patients in group 1 (group 3). RESULTS: Diabetes mellitus was present in 32.3%, 3.6%, and 9.7% of patients in groups 1, 2, and 3, respectively. When compared with controls (group 3), DM was significantly less frequent in group 2 (p < 0.004) and significantly more frequent in group 1 (p < 0.0001). The prevalence of DM was not different among patients with HCV, HBV infection, or alcohol abuse. In group 3, the prevalence of DM appeared to increase steadily with age. On the contrary, in patients with liver cirrhosis (group 1) DM was detected in about 20-30% of cases in all decades of age. In group 2, diabetics were found only in the 7th and 8th decades of life. At multivariate analysis cirrhosis and age were the only two factors independently associated with DM; odds ratios were 12.5 (95% confidence interval [C.I.], 6.74-20.4) for cirrhosis, and 1.47 for age (95% C.I. 0.39-2.55). CONCLUSIONS: Our findings disprove HCV infection as a trigger factor for DM, which should not be listed among the various extrahepatic manifestations of this viral infection.

Adult↗

nm23 expression in human breast cancer: correlation with cell proliferation (S-phase) as observed with a double-labeling immunocytochemical-autoradiographic technique.

In 51 unselected breast cancer samples, a double-labeling immunocytochemical technique was utilized to observe the phenotypic expression of the nm23 gene during S-phase. The feasibility of the method was confirmed by comparison with routine evaluations for both thymidine-labeling index and nm23 (p<0.001). No correlation was found between the two parameters in the overall series or when subgroups regarding menopausal status, nodal involvement, tumor size, hormone receptor content were considered. Tumors with a higher nuclear grade showed a significant correlation only with TLI (p=0. 02). A trend for an inverse relationship between the two parameters was noted but was not statistically significant. A significant association between TLI and nm23 expression was found by Chi-square test using median values as cut-off. Our data based on morphological and in situ observations do not confirm a correlation between nm23 and cell proliferation, even if this correlation cannot be completely excluded. Multicentric trials of high power with these same techniques are still necessary to definitely establish the prognostic role of nm23 in breast cancer.

Adult↗

Timing of breast cancer surgery within the menstrual cycle: tumor proliferative activity, receptor status and short-term clinical outcome.

We verified the variations of primary tumour steroid receptor status and proliferative activity at different times and phases (follicular vs luteal) of the menstrual cycle and their relationship with short clinical outcome in a cohort of 248 N- breast cancer patients. Steroid receptor content (ER and PgR) was evaluated by DCC assay and proliferative activity by 3H-Thymidine autoradiographic assay (TLI). Median age was 44 years, 60% of tumors were T1, and cytohistological grade was G1-2 in 54% of cases. At surgery, 57% were in the luteal phase while 43% were in the follicular phase. No significant variations were found in mean TLI or ER and PgR characteristics of the primary tumors surgically treated in different periods of the menstrual cycle; however, the ER level resulted significantly higher in 4th with respect to the 3rd week of menstrual cycle, while PgR level was higher in PgR+ cases treated during the 3rd week. The number of relapses and disease-free survival curves after 36 months median follow-up did not differ significantly for patients treated in different periods of the menstrual cycle (12% and 9% of disease relapses in luteal and follicular phases; p=n.s.). We can conclude, therefore, that TLI, ER and PgR expressions could vary significantly during menstrual cycle only in certain specific tumor subgroups.

Adult↗

Prolonged treatment (2 years) with different doses (3 versus 6 MU) of interferon alpha-2b for chronic hepatitis type C. Results of a multicenter randomized trial.

BACKGROUND/AIMS: To examine the effect of prolonged treatment with different doses of interferon alpha-2b on the relapse rate in patients with chronic hepatitis C. METHODS: One hundred and seventy-one patients with non-cirrhotic chronic hepatitis C were enrolled in an Italian multicenter trial. All patients were treated for 3 months with 3,000,000 Units (3 MU) of interferon alpha-2b given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine aminotransferase (ALT) values were given 6 MU of interferon for an additional 3 months. If ALT remained persistently abnormal, therapy was then suspended. If ALT levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18 months (total=2 years). Patients with normal ALT were randomly assigned to two groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional 21 months (total=2 years). Follow-up continued for 2 years after therapy withdrawal. RESULTS: Seven patients stopped treatment during the first 3 months. Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a sustained response was maintained in eight during the follow-up. Overall, 54 and 34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and 21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.). After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21 (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to-treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT values, HCV-RNA negative). About 65% of the sustained responders showed low baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b was more frequently found among non-responders than in long-term responders (84% vs 25%, p=0.0001). CONCLUSIONS: About 14% of patients who do not respond to a 3-month course of 3 MU of interferon normalize ALT levels when given 6 MU. In prolonged treatment, there is no significant difference between 3 and 6 MU in inducing a sustained response. Patients with low baseline viremia and genotype 2a respond significantly better to prolonged interferon therapy than highly viremic patients with genotype 1b.

Antiviral Agents↗

HCV genotypes in patients with liver disease of different stages and severity.

UNLABELLED: AIMS/MATERIAL: Hepatitis C virus (HCV) genotyping was performed in 213 anti-HCV-positive patients with chronic liver disease ranging from minimal histological changes to hepatocellular carcinoma. One hundred and twenty-two patients had non-cirrhotic chronic active or persistent hepatitis (including 29 who were asymptomatic with persistently normal ALT levels) (chronic liver disease group). The other 91 had hepatocellular carcinoma and, in all but three cases, cirrhosis (hepatocellular carcinoma group). RESULTS: The overall prevalence of HCV variants was: 54.9% type 1b, 37.8% type 2, 2.5% type 1a, 2.0% type 3a, 2.0% type 4a. The genotype distribution showed no relation to the stage (chronic liver disease vs. hepatocellular carcinoma) or severity (chronic active vs. chronic persistent hepatitis) of the liver disease, or to the duration of the disease (<10 years vs. >10 years). Within the hepatocellular carcinoma group, the duration of type-1b disease was similar to that of type-2 infections. Ages at the time of infection and genotype were both independently associated with progression to cirrhosis and hepatocellular carcinoma, but multivariate analysis revealed that the effect of age was much stronger than that of genotype 1b. CONCLUSIONS: The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our findings indicate that infections caused by each HCV genotype are capable of progressing to hepatocellular carcinoma.

Adolescent↗